Sonographic findings of COVID‐Arm: A case series

Erythematous patches or swollen plaques appearing usually after 4 days or more at the injection site of SARS‐CoV‐2 vaccination are commonly known as ‘COVID‐Arm’. It is considered normal to have signs of inflammation up to 3 days after the vaccine is administered. Pathological inflammatory reactions are those that persist beyond 3 days. COVID‐Arm is one of the most commonly reported adverse effect of all COVID‐19 vaccines, but it seems much more frequent with mRNA‐1273.2–4 COVID‐Arm is almost exclusively described in women. Skin biopsies in COVID‐Arm have shown superficial perivascular and perifollicular lymphocytic infiltrates, with rare eosinophils and scattered mast cells. These findings correspond with a delayed‐type hypersensitivity reaction. High‐frequency ultrasound (HFUS) aids in the diagnosis and follow‐up of inflammatory skin diseases. We describe herein the ultrasound characteristics of local injection‐site cutaneous adverse reactions after vaccination against SARS‐CoV‐2. PATIENTS


INTRODUCTION
Erythematous patches or swollen plaques appearing usually after 4 days or more at the injection site of SARS-CoV-2 vaccination are commonly known as 'COVID-Arm'. 1 It is considered normal to have signs of inflammation up to 3 days after the vaccine is administered. Pathological inflammatory reactions are those that persist beyond 3 days. COVID-Arm is one of the most commonly reported adverse effect of all COVID-19 vaccines, but it seems much more frequent with mRNA-1273. [2][3][4] COVID-Arm is almost exclusively described in women. 5 Skin biopsies in COVID-Arm have shown superficial perivascular and perifollicular lymphocytic infiltrates, with rare eosinophils and scattered mast cells. These findings correspond with a delayed-type hypersensitivity reaction. 6 High-frequency ultrasound (HFUS) 7 aids in the diagnosis and follow-up of inflammatory skin diseases. 8 We describe herein the ultrasound characteristics of local injection-site cutaneous adverse reactions after vaccination against SARS-CoV-2.

PATIENTS
We studied seven patients with COVID-Arm attended in our department between the 1st of March and the 30th of June, 2021. All patients were Caucasian females, with age between 27 and 59 years (median, 37 years). We excluded patients with injection-site reactions lasting ≤3 days, as this reaction was very common in SARS-CoV-2 vaccine randomised controlled trials. 9 The study was authorised by the Ethics Committees of our institution. All patients gave written informed consent to participate and explicit consent to publish images.

TECHNIQUE
HFUS was performed by a dermatologist trained in the diagnosis and management of autoimmune diseases and HFUS. Esaote MyLab™Class C equipment was used with high-frequency probes between 10, 18 and 22 MHz.
The following cut-off values were used to determine negative Doppler: isolated vessels in the dermis and Sonographic findings of COVID-Arm hypodermis, with a systolic peak of <10 cm/s and a resistance index of <0.7. 2,10 Active panniculitis was defined as fulfilment of ≥2 of the three criteria in Doppler mode: systolic peak >10 cm/s, resistance index >0.7 MHz, and vessel diameter >1 mm. The variables analysed in mode B of the HFUS considered to be indicative of inflammation were hypoechogenicity of the dermis, hyperechogenicity of lobes in all cases with or without hypoechogenicity and thickening of the subcutaneous septa. 3,8 Increased or decreased echogenicity was considered in comparison with healthy perilesional and contralateral skin. Septa were considered thickened if 3 or more septa were thicker than 1 mm. 10 Other signs present in active disease were hypoechogenicity of the dermis and loss of the dermo-hypodermal line. 8 Table 1 shows the clinical and HFUS characteristics of patients. In one patient, localised inflammation was observed only in the dermis, without signs of panniculitis ( Figure 1). Inflammation of the hypodermis was observed in six of the seven patients (85.7%); in five (71.4%) cases, the ultrasound pattern was lobular panniculitis and in only one (14.3%) was mixed panniculitis (septal and lobular). Vessel diameter was increased, with a median of 1.4 mm (IQR: 0.8−1.7 mm), and a median peak systolic velocity of 7 cm/s (IQR: 5−15.2 cm/s) (Figures 2-4).

RESULTS
Areas of inflammation were observed with hypoechogenicity of the dermis and hyperechogenicity of lobules in the hypodermis. In addition, in patients with panniculitis, a loss of differentiation between dermis and hypodermis was seen. These findings can be seen in Figures 5 and 6, where the inflamed area is compared with the contralateral healthy skin. In one patient, an enlarged axillary lymph node was observed on the same side of the vaccine application. The node measured 20.1 x 9.3 mm with intense vascularisation distributed from the hilum towards the periphery, had arterial vessels up to 1.2 mm in diameter and a very high velocity (a systolic peak of 37.2 cm/s and resistance index of 0.87) (Figure 7). A characteristic HFUS pattern of inflammation was observed in this patient, with increased flow from the hilum to the periphery.

DISCUSSION
We observed that patients with COVID-Arm had inflammation of the dermis and the hypodermis, with signs of panniculitis, similar to those seen with HFUS in autoimmune and infectious diseases. 10 The colour F I G U R E 2 Case 1. Increased vascularisation in dermis and hypodermis. Arterial vessels with a 9 cm/s systolic peak, diastolic 2.6 cm/s, and a resistance index of 0.71. Doppler mode allowed us to quantify the inflammation and indicate treatment according to clinical and ultrasonographic signs. In addition, other findings such as inflammatory lymph nodes were observed.
COVID-Arm is usually diagnosed on clinical grounds. 1 In most cases, inflammation resolves spontaneously or with topical anti-inflammatory treatment after a few days. 2 Therefore, skin biopsy is usually not necessary. Some patients may have persistent lesions that require longer topical treatment or even oral corticosteroid therapy.
HFUS is a technique that has become widespread in a routine dermatology practice in recent years. 10 It can be carried out at the office and aids in therapeutic decision making, by comparing clinical and imaging findings. In  inflammatory diseases, HFUS is helpful to define the site of involvement (whether dermal, hypodermic, or both) and quantify vascularisation. 8,10 In panniculitis, HFUS has proven helpful in assessing lobular, septal, or mixed patterns. Finally, HFUS permits assessment of response to treatment during follow-up.
In our case series, COVID-Arm affected the deeper layers of the skin. This was demonstrated with HFUS, without the need for a skin biopsy. We propose that HFUS is a useful noninvasive imaging technique for a complete assessment of vaccine reactions.